RESUMO
Although many major breakthrough had identificated potential susceptibility genes for schizophrenia, the aetiology of schizophrenia is still unknown. In the present study, we focused on the N-methyl-Daspartate receptors related genes nitric oxide synthase 1 adaptor gene (NOS1AP), disrupted in schizophrenia 1 gene (DISC1), d-amino acid oxidase activator gene (DAOA), and glycogen synthase kinase 3-beta gene (GSK3B). A family-based genetic association study (459 Han Chinese subjects in 153 nuclear families) using 3 single nucleotide polymorphisms in NOS1AP, 2 in DISC1, 1 in DAOA and 1 in GSK3B was conducted. We found rs12742393 have just positive trend with schizophrenia (SCZ) (p=0.07) after FDR correction. NOS1AP mRNA and serum levels were significantly elevated in SCZ patients (p<0.001; p<0.001) compared with healthy control. However, expression Quantitative Trait Loci (eQTL) analysis have demonstrated that rs12742393 genotype were not significantly associated with the NOS1AP mRNA expression. GMDR identified a significant seven-locus interaction model involving (NOS1AP-rs348624, rs12742393, rs1415263, DISC1-rs821633, rs1000731, DAOA-rs2391191and GSK3B- rs6438552) with a good testing accuracy (0.72). Our finding suggested statistically significant role of interaction of NOS1AP, DISC1, DAOA, and GSK3B polymorphisms (NOS1AP-rs348624, rs12742393, rs1415263, DISC1-rs821633, rs1000731, DAOA-rs2391191and GSK3B-rs6438552) in EOS susceptibility.
Assuntos
Proteínas Adaptadoras de Transdução de Sinal/genética , Proteínas de Transporte/genética , Predisposição Genética para Doença , Glicogênio Sintase Quinase 3 beta/genética , Proteínas do Tecido Nervoso/genética , Esquizofrenia/genética , Proteínas Adaptadoras de Transdução de Sinal/metabolismo , Idade de Início , Povo Asiático/genética , Proteínas de Transporte/metabolismo , China , Epistasia Genética , Família , Feminino , Estudos de Associação Genética , Glicogênio Sintase Quinase 3 beta/metabolismo , Humanos , Peptídeos e Proteínas de Sinalização Intracelular , Masculino , Modelos Genéticos , Proteínas do Tecido Nervoso/metabolismo , Polimorfismo de Nucleotídeo Único , RNA Mensageiro/metabolismo , Esquizofrenia/epidemiologia , Esquizofrenia/etnologia , Esquizofrenia/metabolismo , Adulto JovemRESUMO
Human personality traits differ across geographical regions 1-5 . However, it remains unclear what generates these geographical personality differences. Because humans constantly experience and react to ambient temperature, we propose that temperature is a crucial environmental factor that is associated with individuals' habitual behavioural patterns and, therefore, with fundamental dimensions of personality. To test the relationship between ambient temperature and personality, we conducted two large-scale studies in two geographically large yet culturally distinct countries: China and the United States. Using data from 59 Chinese cities (N = 5,587), multilevel analyses and machine learning analyses revealed that compared with individuals who grew up in regions with less clement temperatures, individuals who grew up in regions with more clement temperatures (that is, closer to 22 °C) scored higher on personality factors related to socialization and stability (agreeableness, conscientiousness, and emotional stability) and personal growth and plasticity (extraversion and openness to experience). These relationships between temperature clemency and personality factors were replicated in a larger dataset of 12,499 ZIP-code level locations (the lowest geographical level feasible) in the United States (N = 1,660,638). Taken together, our findings provide a perspective on how and why personalities vary across geographical regions beyond past theories (subsistence style theory, selective migration theory and pathogen prevalence theory). As climate change continues across the world, we may also observe concomitant changes in human personality.
Assuntos
Personalidade , Temperatura , Adulto , China , Feminino , Humanos , Aprendizado de Máquina , Masculino , Análise Multinível , Análise Espacial , Estados Unidos , Adulto JovemRESUMO
BACKGROUND: Previous studies report that various single nucleotide polymorphisms (SNP) in the Disrupted-in Schizophrenia 1 (DISC1) gene are closely associated with schizophrenia, but there are no studies that assess the relationship of age of onset of schizophrenia with these SNPs. OBJECTIVE: Investigate the relationship between the rs821633 SNP in the DISC1 gene and the occurrence and age of onset of schizophrenia in Han Chinese. METHODS: We used the TaqMan genotyping technology to examine the rs821633 SNP in the DISC1 gene among 315 individuals who developed schizophrenia prior to 19 years of age ('early-onset'), 407 individuals who developed schizophrenia when 19 years of age or older ('late-onset'), and 482 healthy controls. We used survival analyses to investigate the relationship between the rs821633(C) risk allele and the age of onset of schizophrenia. RESULTS: Compared to the prevalence in healthy controls, the prevalence of the C/C genotype of rs821633 and of the C allele in rs821633 were significantly greater in individuals with early-onset schizophrenia (X (2)=7.17, df=1, p=0.007; X (2)=7.20, df=2, p=0.032) and significantly greater in individuals with late-onset schizophrenia (X (2)=5.36, df=1, p=0.022; X (2)=6.58, df=2, p=0.041). However, there were no significant differences in the prevalence of the C/C genotype or the C allele between individuals with early-onset and late-onset schizophrenia. Kaplan-Meier survival analyses found no significant association between the rs821633(C) risk allele and age of onset in schizophrenia. CONCLUSION: We confirm the association of polymorphism in the rs821633 SNP in the DISC1 gene with schizophrenia among Han Chinese, but we found no association between the rs821633(C) risk allele and the age of onset in individuals with schizophrenia.